Sodium Oxybate in Spasmodic Dysphonia and Voice Tremor
Central Mechanisms and Treatment Response of Sodium Oxybate in Spasmodic Dysphonia and Voice Tremor
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Massachusetts Eye and Ear
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Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients with SD and combined SD and VT will have a clinically documented adductor or abductor form of disorder, either with or without positive effects of alcohol on their voice symptoms;
- Healthy controls will be healthy volunteers with a negative history of laryngeal, neurological, or psychiatric problems (existing neuroimaging data will be used);
- Age from 21 to 80 years.
- Native English speakers.
- Right-handedness (based on Edinburgh Handedness Inventory).
Exclusion Criteria:
- Subjects who are incapable of giving an informed consent will be excluded from the study.
- Pregnant and breastfeeding women until a time when they are no longer pregnant or breastfeeding will be excluded from the study. All patients of childbearing potential will be required to agree to use a reliable method of contraception prior to and during the study. The method of contraception will be documented in the patient's research chart. All women of childbearing potential will undergo a urine pregnancy test, which must be negative for study participation.
All patients with a past or present history of the following conditions will be excluded from the study;
- Except for SD and dystonic VT, any neurological disorders, such as stroke, movement disorders, brain tumors, traumatic brain injury with loss of consciousness, ataxias, myopathies, myasthenia gravis, demyelinating diseases, alcoholism, drug dependence. Patients with tremor affecting other body parts will be excluded from the study. All patients who have dystonic movements in the body regions other than the larynx will be excluded from the study. This will allow maintaining the homogenous patient population and evaluating central drug effects without confounding by the presence of other neurological conditions.
- Any psychiatric problems, such as schizophrenia, major and/or bipolar depression, obsessive-compulsive disorder, will be excluded to maintain the homogenous patient population and allow for the evaluation of central drug effect without confounding by the presence of psychiatric conditions.
- Any laryngeal problems, such as vocal fold paralysis, paresis, carcinoma, chronic laryngitis, will be excluded from the study.
- Patients with a known past or present history of grade 2 or higher hepatic and renal dysfunction according to the NCI criteria will be excluded.
- Patients with a known past or present history of moderate to severe congestive heart failure will be excluded.
- Patients with a known past or present history of cognitive impairment and active suicidal ideations will be excluded.
- Patients who are not symptomatic due to treatment with botulinum toxin injections into the laryngeal muscles will be excluded from the study until the time when they are fully symptomatic. The duration of positive effects of botulinum toxin vary from patient to patient, lasting on average 3-4 months. All patients will be evaluated to ensure that they are fully symptomatic prior to the entering the study.
- To avoid the possibility of confounding effects of drugs acting upon the central nervous system, all patients will be questioned about any prescribed or over-the-counter medications as part of their initial intake screening. Those patients who receive medication(s) affecting the central nervous system (except for sodium oxybate) will be excluded from the study.
- Patients will be asked whether they have undergone any head and neck surgeries, particularly any brain surgery and laryngeal surgeries, such as thyroplasty, laryngeal denervation, and selective laryngeal adductor denervation-reinnervation. Because both brain and laryngeal surgery may potentially lead to the brain structure and function re-organization, all subjects with a history of brain and/or laryngeal surgery will be excluded from the study.
- Patients who have tattoos, ferromagnetic objects in their bodies (e.g., implanted stimulators, surgical clips, prosthesis, artificial heart valve, etc.) that are not MRI comparable and/or cannot be removed for the purpose of MRI study participation will be excluded from the study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
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Experimental: Clinical response to sodium oxybate
In contrast to placebo but similar to alcohol, sodium oxybate is expected to be most effective in reducing voice symptoms in alcohol-responsive SD and VT.
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Alcohol challenge test and oral administration of a single dose of sodium oxybate and the matching placebo.
Other Names:
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Experimental: Central markers of clinical response
The clinical outcome is expected to be determined by selective modulation of functional abnormalities in the brain regions controlling speech sensorimotor processing and integration in association with underlying gene variants.
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Alcohol challenge test and oral administration of a single dose of sodium oxybate and the matching placebo.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Symptom Severity
Time Frame: 40 min after drug or placebo administration
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A combined clinician-objective and patient-subjective change in visual analog scale (min-max 0-100, a higher score is the worse outcome) score of symptom severity before and after drug vs. placebo intake. For analysis, patients in groups (1) Alcohol-responsive (EtOH+) Laryngeal Dystonia and (2) Alcohol-responsive (EtOH+) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH+ group. For analysis, patients in groups (3) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia and (4) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH- group. |
40 min after drug or placebo administration
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Minimum Treatment Efficacy
Time Frame: 40 min after drug or placebo administration
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Pre-specified to analysis based only on alcohol responsiveness (EtOH+).
A combined clinician-objective and patient-subjective change in visual analog scale score (min-max 0-100, a higher score is the worse outcome) of symptom severity in EtOH+ patients.
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40 min after drug or placebo administration
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Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Treatment Efficacy Dependent on LD Clinical Type
Time Frame: 40 min after drug or placebo administration
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A combined clinician-objective and patient-subjective change in visual analog scale (min-max 0-100, a higher score is the worse outcome) score of symptom severity before and after drug vs. placebo intake. EtOH+ and EtOH- were stratified based on phenotypical characteristics, including LD, LD with Dystonic Tremor of Voice, Abductor LD, Adductor LD. |
40 min after drug or placebo administration
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Length of Treatment Efficacy
Time Frame: 40 min to 5 hours after drug or placebo administration
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The length of treatment efficacy in each EtOH+ and EtOH- group was assessed at 40, 180, and 300 min after drug vs. placebo intake compared to the baseline using a combined clinician-objective and patient-subjective change in visual analog scale (min-max 0-100, a higher score is the worse outcome) score of symptom severity. For analysis, patients in groups (1) Alcohol-responsive (EtOH+) Laryngeal Dystonia and (2) Alcohol-responsive (EtOH+) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH+ group. For analysis, patients in groups (3) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia and (4) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH- group. |
40 min to 5 hours after drug or placebo administration
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Relationship Between Alcohol-responsiveness of Symptoms and Drug-induced Symptom Improvement
Time Frame: 40 min after drug or placebo administration
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A combined clinician-objective and patient-subjective change in visual analog scale (min-max 0-100, a higher score is the worse outcome) score of symptom severity before and 40 min after drug vs. placebo intake. For analysis, patients in groups (1) Alcohol-responsive (EtOH+) Laryngeal Dystonia and (2) Alcohol-responsive (EtOH+) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH+ group. For analysis, patients in groups (3) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia and (4) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH- group. |
40 min after drug or placebo administration
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Relationship Between Symptom Severity Change and Dystonia Clinical Characteristics
Time Frame: 40 min after drug or placebo administration
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A combined clinician-objective and patient-subjective change in visual analog scale (min-max 0-100, a higher score is the worse outcome) score of symptom severity before and 40 min after drug vs. placebo intake. For analysis, patients in groups (1) Alcohol-responsive (EtOH+) Laryngeal Dystonia and (2) Alcohol-responsive (EtOH+) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH+ group. For analysis, patients in groups (3) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia and (4) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH- group. |
40 min after drug or placebo administration
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Collaborators and Investigators
Sponsor
Sponsor
Collaborators
Collaborators
Investigators
Investigators
- Principal Investigator: Kristina Simonyan, MD, PhD, Massachusetts Eye and Ear
Publications and helpful links
General Publications
- Simonyan K, Ludlow CL. Abnormal activation of the primary somatosensory cortex in spasmodic dysphonia: an fMRI study. Cereb Cortex. 2010 Nov;20(11):2749-59. doi: 10.1093/cercor/bhq023. Epub 2010 Mar 1.
- Simonyan K, Frucht SJ. Long-term Effect of Sodium Oxybate (Xyrem(R)) in Spasmodic Dysphonia with Vocal Tremor. Tremor Other Hyperkinet Mov (N Y). 2013 Dec 9;3:tre-03-206-4731-1. doi: 10.7916/D8CJ8C5S. eCollection 2013.
- Rumbach AF, Blitzer A, Frucht SJ, Simonyan K. An open-label study of sodium oxybate in Spasmodic dysphonia. Laryngoscope. 2017 Jun;127(6):1402-1407. doi: 10.1002/lary.26381. Epub 2016 Nov 3.
- Battistella G, Fuertinger S, Fleysher L, Ozelius LJ, Simonyan K. Cortical sensorimotor alterations classify clinical phenotype and putative genotype of spasmodic dysphonia. Eur J Neurol. 2016 Oct;23(10):1517-27. doi: 10.1111/ene.13067. Epub 2016 Jun 27.
- Kirke DN, Battistella G, Kumar V, Rubien-Thomas E, Choy M, Rumbach A, Simonyan K. Neural correlates of dystonic tremor: a multimodal study of voice tremor in spasmodic dysphonia. Brain Imaging Behav. 2017 Feb;11(1):166-175. doi: 10.1007/s11682-016-9513-x.
- Kirke DN, Frucht SJ, Simonyan K. Alcohol responsiveness in laryngeal dystonia: a survey study. J Neurol. 2015 Jun;262(6):1548-56. doi: 10.1007/s00415-015-7751-2. Epub 2015 May 1.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Actual)
Primary Completion
Study Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Estimated)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neurologic Manifestations
- Nervous System Diseases
- Respiratory Tract Diseases
- Otorhinolaryngologic Diseases
- Laryngeal Diseases
- Voice Disorders
- Pathological Conditions, Signs and Symptoms
- Signs and Symptoms
- Dysphonia
- Organic Chemicals
- Acids, Acyclic
- Carboxylic Acids
- Hydroxy Acids
- Alcohols
- Butyrates
- Hydroxybutyrates
- Ethanol
- Sodium Oxybate
Other Study ID Numbers
Other Study ID Numbers
- 2019P001680
- R01DC012545 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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